A 45-year-old man with a low titer of hepatitis B virus (HBV) was diagnosed with nephrotic syndrome. A subsequent test for human immunodeficiency virus (HIV) was positive. Kidney biopsy revealed some signs of collapsing variant of focal segmental glomerulosclerosis (FSGS), but the predominant finding was a cellular variant of FSGS. Two years after receiving tenofovir, urine protein became negative, and the patient was finally diagnosed with HIV-associated nephropathy. Collapsing variant of FSGS is considered typical of HIV-related nephropathy, but the cellular variant of FSGS in this patient represents another type. The cause of many FSGSs is often never identified, making cause-based treatment difficult. This case demonstrates that identification of the cause of FSGS can lead to treatment of FSGS.

This article is devoted to managing posterior ankle impingement syndrome and its management using endoscopic to arthroscopic surgical instrumentation. The authors explore the critical anatomy, pathogenesis, and clinical examination. Operative techniques, including the approach, and instrumentation used, are outlined. The postoperative protocol is discussed. Finally, a literature review is provided, which also defines known complications.

The plantar plate is a critical structure involved in stabilizing the metatarsophalangeal joint. Its disruption can not only be painful for the patient but also may lead to subsequent structural deformities. There are several conservative treatment modalities available to help mitigate symptoms including splinting, offloading, and intraarticular injections. That being said, once the pathology progresses to advanced stages, these treatments are not efficacious. Reported success with conservative treatment modalities is limited to case studies and series with a low level of clinical evidence. As such, this represents an area where further investigation is needed to evaluate the true efficacy of conservative treatment and to allow for development of a more standardized approach.

Reproductive genetic carrier screening aims to offer couples information about their chance of having children with certain autosomal recessive and X-linked genetic conditions. We developed a gene list for use in "Mackenzie's Mission", a research project in which 10,000 couples will undergo screening. Criteria for selecting genes were: the condition should be life-limiting or disabling, with childhood onset, such that couples would be likely to take steps to avoid having an affected child; and/or be one for which early diagnosis and intervention would substantially change outcome. Strong evidence for gene-phenotype relationship was required. Candidate genes were identified from OMIM and via review of 23 commercial and published gene lists. Genes were reviewed by 16 clinical geneticists using a standard operating procedure, in a process overseen by a multidisciplinary committee which included clinical geneticists, genetic counselors, an ethicist, a parent of a child with a genetic condition and scientists from diagnostic and research backgrounds. 1300 genes met criteria. Genes associated with non-syndromic deafness and non-syndromic differences of sex development were not included. Our experience has highlighted that gene selection for a carrier screening panel needs to be a dynamic process with ongoing review and refinement.

Interpretation of the significance of maternally inherited X chromosome variants in males with neurocognitive phenotypes continues to present a challenge to clinical geneticists and diagnostic laboratories. Here we report 14 males from 9 families with duplications at the Xq13.2-q13.3 locus with a common facial phenotype, intellectual disability (ID), distinctive behavioral features, and a seizure disorder in two cases. All tested carrier mothers had normal intelligence. The duplication arose de novo in three mothers where grandparental testing was possible. In one family the duplication segregated with ID across three generations. RLIM is the only gene common to our duplications. However, flanking genes duplicated in some but not all the affected individuals included the brain-expressed genes NEXMIF, SLC16A2, and the long non-coding RNA gene FTX. The contribution of the RLIM-flanking genes to the phenotypes of individuals with different size duplications has not been fully resolved. Missense variants in RLIM have recently been identified to cause X-linked ID in males, with heterozygous females typically having normal intelligence and highly skewed X chromosome inactivation. We detected consistent and significant increase of RLIM mRNA and protein levels in cells derived from seven affected males from five families with the duplication. Subsequent analysis of MDM2, one of the targets of the RLIM E3 ligase activity, showed consistent downregulation in cells from the affected males. All the carrier mothers displayed normal RLIM mRNA levels and had highly skewed X chromosome inactivation. We propose that duplications at Xq13.2-13.3 including RLIM cause a recognizable but mild neurocognitive phenotype in hemizygous males.